Twist Expression In Circulating Hepatocellular Carcinoma Cells Correlates With Metastasis And Prognoses

Aim:To evaluate the relationship between Twist expression in circulating tumor cells(CTCs),and clinico-histopathologic risk factors of hepatocellular carcinoma(HCC).Background:Hepatocellular carcinoma(HCC)is one of the leading malignancies worldwide.Enumeration of circulating tumor cells(CTCs)has been demonstrated to be a prognostic indicator in HCC.Twist plays a critical role in metastasis,and has been proposed as a biomarker for epithelial-mesenchymal transition(EMT).Patients and methods:Between June 2015 and Septenber 2017,80 HCC patients and 10 healthy volunteers were enrolled in this study.CTCs were isolated and analyzed by the optimized CanPatrolTMCTC-enrichment technique,which isolates and identifies CTCs by a filter-based method and RNA in situ hybridization(RNA-ISH)technology.CTCs and Twist+ CTCs were analyzed for associations with clinico-histopathologic risk factors of HCC patients.Results:CTCs were detected in 62 of the 80(77.5%)HCC patients.No CTCs were detected in any of the blood samples from healthy volunteers.Our analysis showed that CTCs positively correlated with portal vein tumor thrombi(x2=4.267,P=0.039),and tumor number(X2=4.2 19,P=0.04).Twist+ CTCs were detected in 54 of the 80(67.5%)HCC patients.The positive ratios of Twist﹢CTCs correlated with portal vein tumor thrombi(X2=11.483,P=0.001),TNM staging(American Joint Committee on Cancer TNM Staging for Liver Tumors(7th edition,2010))(x2=8.435,P=0.038),AFP(x2=8.724,P=0.033),cirrhosis(X2=11.091,P=0.001),tumor number(X2=12.321,P<0.001)。tumor size(X2=8.021,P=0.018),microvascular invasion(x2=9.616,P=0.004),and Glypican-3 protein(x2=8.050,P=0.005).Meanwhile,the follow-up results of 33 HCC patients received resection of liver cancer showed that the positive ratios of Twist+ CTCs were closely correlated with the rate of metastasis or recurrence(x2=11.806,P=0.001)and the mortality rate(X2=12.165,P=0.0001).The ROC curve analyse suggested that the prognostic evaluation of Twist+ CTCs outperforms CTCs alone.Conclusion:Twist expression in CTCs could serve as a biomarker for evaluating HCC metastasis and prognosis.EMT plays an important role in promoting dissemination of HCC cells.